Estrone-cyclo-ethanolamine



Patented June 19, 1951 UNITED STATES PATENT OFFICE ESTRONE-CYCLO-ETHANOLAMINE Halfdan Hebo, New York, N. Y.

N Drawing. Application August 28, 1948, Serial N 0. 46,710

1 Claim. (Cl. 260-239.5)

l 2 This invention relates to new derivatives of the the process is about 90 percent completed, defemale sex hormone: estrone. pending upon the purity of the original estrone.

These new estrone compounds consist of the The new derivative crystallizes out in small, uniestrone molecule to which has been added ethform, bacillus-shaped crystals, plainly visible to anolamine (HzNCHzCHzOH) at various positions 5 the naked eye.

of the estrone molecule. The crystals are removed from the mother The ethanolamine compound may under cerliquor by vacuum filtration and are washed free tain conditions form a cyclic addition to the kefrom the mother liquor by cold methanol or water tone position or 17th position of the estrone moleor other ethanolamine-miscible solvent, which cule. These new estrone derivatives have proved does not dissolve the newly formed compound. to be extraordinarily active when administrated The non-reacted estrone in the mother liquor orally, Biological experiments, using standard may be recovered by addition of a concentrated rats indicate that the response to these comsolution of sodium bicarbonate, which precipipounds is about ten times that of estrone, when tates the non-reacted estrone from the ethanolboth are administrated orally. Thus, when five amine.

micrograms of the ethanolamine compound was The estrone-cyclo-ethanolamine is almost inadministrated to rats orally the response was soluble in ether and isopropyl ether, slightly solgreater than when 50 micrograms of estrone was uble in water and methanol. It may be recrysgiven to other rats under similar condition when tallized by dissolving it in about 200 parts of hot tested by the modified method of Khant and methanol and after chilling to about 4 degrees Doisy (Endocrinology, vol. 12, page 760; 1928). centigrade and addition of one volume of water, The derivatives of estrone may be made the estrone-cyclo-ethanolamine will slowly begin to following way: crystallize out in uniform, bacillus-shaped crys- One gram of estrone, either pure or crude, is tals. The crystals have a melting point of 251- dissolved in about ten grams of ethanolamine. 253 centigrade. Hereby a new compound is formed, consisting of I claim: the estrone molecule with a molecule of ethanol- The compound having the structural formula: amine attached at the phenolic position of the (FOHPCH estrone. This compound is readily soluble in water. --N

By heating of the estrone-ethanolamine compound, made as described above, to about 80 degrees centigrade, another compound is formed; the ethanolamine group is being transferred to the ketonic position of the estrone molecule (the 110 17th position).

By continuous heating at about 80 degrees cen- HAIFDAN HERO. tigrade, the added ethanolamine group at the ketonic position will cyclise under the separation of one water molecule and form the following REFERENCES CITED compound: The following references are of record in the CH8 (FCHFCH file of this patent:

NH UNITED STATES PATENTS Number Name Date 2,047,307 Butenandt July 14, 1936 2,055,083 Klein et al Sept. 22, 1936 2,219,791 Robald et al Oct. 29, 1940 H0 FOREIGN PATENTS This compound crystallizes out after a few min- Number Country Date utes of heating and after about 20-50 minutes 676,115 Germany May 26, 1939 

